Lynch Mark B, Lawrence Simon E, Nolan Michael
Department of Chemistry, Analytical and Biological Chemistry Research Facility, Synthesis and Solid State Pharmaceutical Centre , University College Cork , Cork , Ireland.
Tyndall National Institute , University College Cork , Lee Maltings Complex, Dyke Parade , Cork , Ireland.
J Phys Chem A. 2018 Mar 29;122(12):3301-3312. doi: 10.1021/acs.jpca.8b01342. Epub 2018 Mar 15.
The interactions of isonicotinamide (INA) with seven common solvents (acetic acid, acetonitrile, acetone, chloroform, ethyl acetate, and methanol) have been studied to examine solute-solvent effects on the nucleation of INA from these solvents. In a simple model of 1:1 solute-solvent interactions, the strongest INA-solvent interaction is with acetic acid (binding energy, Δ E = -64.05 kJ mol) and the weakest is with chloroform (Δ E = -24.85 kJ mol). This arises since acetic acid and INA form a hydrogen-bonding motif containing two moderate strength N-H···O hydrogen bonds, while chloroform and INA have a single weak C-H···O hydrogen bond. Taking acetic acid, chloroform, and methanol, the solvents with the strongest, the weakest, and an intermediate strength INA-solvent binding energy, the solvation of INA was studied to compare it with the 1:1 model. Acetic acid has the strongest binding energy (-872.24 kJ mol) and solvation energy (-341.20 kJ mol) with chloroform binding energy (-517.72 kJ mol) and solvation energy (-199.05 kJ mol). Methanol has intermediate binding energy (-814.19 kJ mol) and solvation energies (-320.81 kJ mol). These results further confirm the recent the findings which indicate that the key trends in solvent-solute interactions can be determined from a simple and efficient 1:1 dimer model and can be used to predict ease of nucleation with stronger binding energies correlating to slower, more difficult nucleation. A limit of this model is revealed by considering alcohol and acid solvents with longer alkyl chains.
已研究了异烟酰胺（INA）与七种常见溶剂（乙酸、乙腈、丙酮、氯仿、乙酸乙酯和甲醇）之间的相互作用，以考察溶质 - 溶剂对INA从这些溶剂中结晶成核的影响。在1:1溶质 - 溶剂相互作用的简单模型中，INA与溶剂之间最强的相互作用是与乙酸（结合能，ΔE = -64.05 kJ/mol），最弱的是与氯仿（ΔE = -24.85 kJ/mol）。这是因为乙酸和INA形成了一个包含两个中等强度N - H···O氢键的氢键模式，而氯仿和INA只有一个弱的C - H···O氢键。以乙酸、氯仿和甲醇为例，这三种溶剂分别具有最强、最弱和中等强度的INA - 溶剂结合能，研究了INA的溶剂化作用并与1:1模型进行比较。乙酸具有最强的结合能（-872.24 kJ/mol）和溶剂化能（-341.20 kJ/mol），氯仿的结合能为（-517.72 kJ/mol），溶剂化能为（-199.05 kJ/mol）。甲醇具有中等的结合能（-814.19 kJ/mol）和溶剂化能（-320.81 kJ/mol）。这些结果进一步证实了最近的研究发现，即溶剂 - 溶质相互作用的关键趋势可以通过一个简单有效的1:1二聚体模型来确定，并且可以用于预测成核的难易程度，结合能越强，成核越慢、越困难。通过考虑具有较长烷基链的醇类和酸类溶剂，揭示了该模型的一个局限性。
